ABSTRACT: BACKGROUND:With multiple cholesterol guidelines, we evaluated the accuracy of recommended statin therapy on identifying coronary artery calcium (CAC) and cardiovascular disease (CVD) events by 2004 NCEP/ ATP III, 2016 ESC/EAS, and 2013 ACC/AHA guidelines. HYPOTHESIS:ACC/AHA guidelines are more accurate in identifying persons at risk for CVD. METHODS:5002/6814 participants age <75 years and free of CVD were included. CAC categories (>0, ?100, and ?300) and 10 years of CVD outcomes were considered. Sensitivity (SN), specificity (SP), positive and negative predictive value (PPV and NPV), and likelihood ratios (LR) were calculated. Mean age was 59 years; 47% of subjects were males. RESULTS:1297 (26%), 1381 (28%), and 2538 (51%) had class I indications for statin/LLT by the NCEP ATP III, ESC/EAS, and AHA/ACC guidelines, respectively. SN, SP, NPV, and PPV for CAC ?300 were: NCEP ATP III (41.1%, 75.5%, 93.3% and 13.4%), ESC/EAS (54.1%, 74.8%, 94.6% and16.6%), and ACC/AHA (87.2%, 52.6%, 97.8% and 14.5%). SN, SP, PPV, and NPV for corresponding CVD outcomes were: NCEP ATP III (45.8%, 75.1%, 96.3%, and 8.9%), ESC/EAS (50.5%, 72.9%, 98.7%, and 3.6%), and AHA/ACC (79.6%, 50.7%, 98%, and 7.7%). ESC/EAS had significantly higher positive LR 2.15 (95% CI, 1.95 - 2.38) and ACC/AHA had significantly lower negative LR [0.24, (95% CI 0.19 - 0.31)] for corresponding CVD. CONCLUSIONS:Despite the increased in SN of statin eligibility by the ACC/AHA, it has similar NPV and PPV for CAC/future CVD events. The ACC/AHA class I indications for statin may be a superior screening tool for subclinical and clinical CVD.